JP2008039635A - Viscoelasticity measuring instrument - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a viscoelasticity measuring instrument for measuring the elasticity and viscosity of a measuring target easy to move and easy to receive heat damage in a non-contact and non-invasive state. <P>SOLUTION: The viscoelasticity measuring instrument is equipped with an exciting laser beam source 10 for emitting an exciting laser beam, an optical system 20 for condensing an exciting beam to a measuring target 30 to capture the scattering light emitted from the measuring target, light condensing position moving means 201 and 202 for moving a condensing position, a condensing position measuring means 50 for measuring the light condensing position, a spectrum analyzer 40 for photoelectrically converting the captured scattering light and measuring the spectrum of the scattering light and a calculator 407 for calculating Brilluane frequency shift and Brilluane line width from the spectrum. The scattering light is a periodic light pulse row and detected in synchronous relation of the optical pulse row. If this instrument is adapted to a living body, a health state can be diagnosed. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an apparatus for measuring the elasticity and viscosity of a measurement object susceptible to thermal damage in a non-contact and non-invasive manner, for example, elastic viscosity measurement capable of diagnosing a health condition based on the elasticity and viscosity of a living body. Relates to the device.

  Conventional techniques such as ultrasonic elastography, MR elastography, photoacoustic viscoelastometry, and OCT elastography are known as elastic / viscous diagnostic techniques. However, in ultrasonic elastography, it is necessary to bring an ultrasonic probe or an ultrasonic transmission medium (such as water or grease) into contact with an object to be measured. In MR elastography, it is necessary to bring a transducer for exciting a pressure wave into contact with an object to be measured. In photoacoustic viscoelastometry, it is necessary to bring a piezoelectric transducer into contact with a measurement object in order to measure a photoacoustic wave. Also in the OCT elastography, it is necessary to contact a means for applying stress to the measurement object.

  On the other hand, Brillouin spectroscopy is known as a technique for measuring elasticity and viscosity without contact. Brillouin spectroscopy is a measurement technique in which excitation light is irradiated onto a measurement object and the spectrum of the generated Brillouin scattered light is analyzed. Brillouin spectroscopy for tissue specimens separated from a living body is known, for example, Non-Patent Document 1 (N. Berovic, et al, Eur. Biophys. J. Vol. 17, pp. 69-74 (1989)). Non-Patent Document 2 (J. Randall, et al., Proc. R. Soc. Lond. Vol. B214, pp. 449-470 (1982)).

N. Berovic, et al, Eur. Biophys. J. Vol. 17, pp. 69-74 (1989) J. Randall, et al., Proc. R. Soc. Lond. Vol. B214, pp. 449-470 (1982)

Brillouin scattering is light scattering by elastic waves in a substance. Scattered light having frequencies of ν + f _B and ν−f _B is generated with the light frequency of excitation light being ν, and they are called anti-Stokes light and Stokes light, respectively. The frequency shift amount f _B is called Brillouin frequency shift and is given by the following equation.

Here, λ is the excitation light wavelength, n is the refractive index of the measurement object at the excitation light wavelength, and θ is the scattering angle. Further, v _a is the acoustic velocity of the acoustic wave is given by the following equation.

Here, c ₁₁ is 11 components of the elastic matrix, and ρ ₀ is the medium density. The scattered light line width Δf _B is given by the following equation.

Here, η _S and η _b are shear viscosity and bulk viscosity, respectively. In this way, by measuring the Stokes light or anti-Stokes light of the Brillouin scattered light and measuring the Brillouin frequency shift and the line width, information on the elasticity and viscosity of the measurement object can be obtained.

However, Brillouin spectroscopy was not performed on the living body itself. This is because, in conventional Brillouin spectroscopy, the measurement time is as long as several minutes, and the power of the excitation light is high.
Therefore, the present invention discloses a Brillouin spectrometer capable of analyzing even a living body itself.

  That is, the problem to be solved by the present invention is that a measuring device that measures the elasticity and viscosity of a measurement object that is susceptible to movement or thermal damage in a non-contact and non-invasive manner, and a health condition based on the elasticity and viscosity of a living body To realize an early diagnosis of arteriosclerosis and cerebral infarction by diagnosing the elasticity of the fundus blood vessel.

In order to achieve the above object, a measuring apparatus according to the present invention comprises:
An excitation laser light source for generating excitation light;
An optical system that collects the excitation light at the collection position of the measurement target and captures the scattered light generated in the measurement target;
An elastic viscosity measuring device comprising a spectrum analyzing means for measuring a spectrum of the scattered light that has been captured and calculating at least one of a Brillouin frequency shift or a Brillouin line width from the spectrum,
The excitation light is a periodic optical pulse train, and the scattered light is detected in synchronization with the optical pulse train (claim 1).
It is preferable to further include a condensing position measuring means for measuring the condensing position of the excitation light.

The spectrum analysis means has storage means for accumulating the power of the spectrum of the scattered light and storing it in a different storage area for each condensing position,
The condensing position measuring means measures a change in the condensing position due to the movement of the measurement object,
It is preferable that the measured spectrum power of the scattered light is accumulated and stored in the storage area of the storage unit corresponding to the condensing position measured by the condensing position measuring unit.

An elastic viscosity measuring device that detects scattered light from a plurality of condensing positions almost simultaneously,
The optical system condenses the excitation light at a plurality of condensing positions in a time-sharing manner,
It is preferable that the spectrum analysis unit integrates the spectrum power of the scattered light from each condensing position.
It is preferable that a spot radius of the excitation light at the condensing position is 3 μm or less.

Wavefront measuring means for measuring the wavefront of scattered light from the measurement object;
An adaptive optics system for adjusting the wavefront of the excitation light,
It is preferable to control the adaptive optics system so that the wavefront measured by the wavefront measuring unit is flat.

An imaging means for taking an image of the measurement object and measuring a condensing position of the excitation light;
Image processing means for extracting feature points of the measurement object from the image,
It is preferable to move the condensing position based on the feature points.

Distance measuring means for measuring a distance in the optical axis direction between the optical system and the measurement object;
It is preferable to provide a computer that extracts a reference point in the depth direction from the distribution of the scattered light power in the optical axis direction.

The measurement object is a fundus blood vessel,
It is preferable to have means for comparing at least one of the Brillouin frequency shift or the Brillouin line width of the scattered light spectrum from the fundus blood vessel with the measurement value of a healthy person (claim 9).

The excitation light has a repetition frequency of f [kHz], a pulse width of t [ns], a wavelength of λ [nm], and an average power of P [dBm].
f> 50
t> 0.28
700 <λ <1100
P <0.02 (λ−700) −1.6
P <5.4
It is preferable that all the conditions are satisfied (claim 10).

  By adopting the above-described configuration, the present invention can effectively measure elasticity and viscosity in a non-contact and non-invasive manner even for a measurement object that is susceptible to movement or optical damage. In particular, even if the measurement target is the fundus of a living body, the elasticity of the fundus blood vessel can be measured without risk of thermal damage to the measurement target, and early diagnosis of arteriosclerosis and cerebral infarction can be realized.

In particular, by using a periodic optical pulse train (Claim 1), the total amount of irradiation energy can be reduced compared to continuous laser irradiation, and the adverse effects of the laser beam on the measurement target can be reduced, and each optical pulse can be reduced. Since the irradiation intensity (power) can be increased, a sufficient SN ratio can be ensured. The maximum allowable exposure amount (MPE) of the laser beam for the human body is defined in JIS C6802, but by making the excitation light a periodic optical pulse train, it is effective within the range of the maximum allowable exposure amount (MPE). Brillouin scattered light can be measured. Furthermore, when the excitation light is an optical pulse train described in claim 10, Brillouin scattered light can be measured most effectively within the range of the maximum permissible exposure (MPE).
Further, by providing the condensing position measuring means (Claim 2), the condensing position can be accurately moved to the target position even for an irregularly shaped measuring object such as a living body. In the case of a conventional tissue specimen, since the measurement target is arranged at a predetermined position, the optical system coordinates coincide with the measurement target coordinates. I was able to move to the place. In the present invention, since the condensing position measuring means for obtaining the condensing position in the measurement object is provided, it is possible to perform Brillouin spectroscopy measurement even on a measurement object whose optical system coordinates and measurement object coordinates do not match, such as a living body. Became.
Furthermore, even if the living body moves and the light collecting position is shifted by the light collecting position measuring means (Claim 2), the measurement data can be corrected by detecting the shift of the light collecting position. Conventionally, only Brillouin spectroscopy such as a tissue specimen that does not move can be measured. However, in the present invention, since the focusing position measuring means detects the deviation of the focusing position, even a measurement object such as a living body can perform Brillouin spectroscopy. Measurement is now possible.

Also, integrating the scattered light spectrum of that part with the condensing position as one point lengthens the laser exposure time of that part and adversely affects the measurement object, but condenses the excitation light at multiple condensing positions in a time-sharing manner. By integrating each of the spectrum power of the scattered light from each condensing position (claim 4), a plurality of condensing positions can be made to be condensed alternately at a plurality of condensing positions. Thus, since the laser exposure amount (per unit time) for each condensing position is reduced, adverse effects on the measurement target can be reduced.
Further, the wavefront measuring means and the compensation optical system (Claim 6) suppress an increase in the spot diameter at the condensing position due to the aberration of the crystalline lens or the optical system. By reducing the spot diameter of the laser, Brillouin scattering can be accurately measured even for a small measurement object such as a fundus arteriole.
Further, by comparing at least one of the Brillouin frequency shift or the Brillouin line width of the scattered light spectrum from the fundus blood vessel with the measurement value of a healthy person (claim 9), it becomes possible to measure the elasticity of the blood vessel. Early diagnosis of diseases and cerebrovascular dementia becomes possible.

Hereinafter, an example of an embodiment of the present invention will be described with reference to the drawings.
FIG. 1 shows a simplified configuration of the elastic-viscosity measuring apparatus of this example, in which 10 is a laser light source, 20 is an optical system, 30 is an object to be measured, 40 is a spectrum analyzer (spectrum analysis means), and 50 is irradiated. Position measuring device (condensing position measuring means), 60 is an adaptive optical system, 70 is a display, 201a and 201b are movable mirrors (condensing position moving means), 202 is a movable lens (condensing position moving means), and 404 is a memory 407 and 505 are computers, 501 is a camera (imaging means), 503 is a laser range finder (distance measuring means), and 602 is a wavefront sensor (wavefront measuring means).

The laser light source 10 emits a pulse train of the excitation light 101. The excitation light 101 is applied to the measurement object 30 via the optical system 20. The irradiation position (condensing position) is controlled and measured by the irradiation position measuring instrument 50, and the measured value is stored in the storage device 404 as an address signal 406a.
Scattered light is generated in the measurement object 30. The scattered light backscattered in the direction of θ = 180 degrees enters the spectrum analyzer 40 via the optical system 20, and the spectrum analyzer 40 measures the Brillouin frequency shift and the line width. The measured value is recorded in the storage device 404 together with the irradiation position (address signal 406b).

The laser light source 10 emits pulsed light having a pulse width τ, a repetition frequency f _r , and a peak power P. These pulse parameters are desirably selected so that the S / N ratio of the measurement is the best within a range where the optical damage of the measurement target does not occur. The present invention discloses the range of such pulse parameters as follows.

First, JIS C6802 is known as a guideline based on various measurement results regarding optical power that is allowed to be irradiated on a living tissue. The contents are extracted and shown in FIG. FIG. 2 is a table summarizing the maximum allowable exposure amount (MPE) of laser light incident on the eye. The value of power is the value of power incident on an iris having a diameter of 7 mm. The spread angle of the laser beam is smaller than the viewing angle, and it is assumed that substantially all of the laser beam power is incident on the iris.
As disclosed in JIS C6802, assuming that the pulse width (exposure time) is τ, the repetition frequency is f _r , and the number of pulses is N,
(Requirement 1) The energy of a single pulse is less than or equal to MPE at the exposure time τ,
(Request 2) MPE in the N duration N / _{f r} of total energy pulse train of pulses below,
(Request 3) A value obtained by multiplying the energy of a single pulse by N ^{0.25 is} equal to or less than MPE at the exposure time τ.
It is necessary to satisfy the following three items.

On the other hand, in the present invention, as will be described later, the synchronization signal 102 synchronized with the repetition frequency of the pulse train of the Brillouin scattered light is detected by the synchronization detector 403, and the data signal 405 is obtained together with the measured values of the Brillouin frequency shift and the line width. And stored in the storage device 404. Therefore, if the average power of the pumping light is P _a , the Brillouin scattering reflectance is R, the optical system loss is a, the photoelectric conversion efficiency is η, the optical frequency is ν, the Planck constant is h, and the electronic charge is e, The current i _S is

It becomes. On the other hand, shot noise is dominant with respect to noise, and if the bandwidth of synchronization detection is Δf, the noise current i _N is

It becomes. Therefore, the signal-to-noise ratio is

It becomes. That is, the S / N ratio is improved in proportion to the average power of the excitation light.

FIG. 3 shows the dependence of the allowable pumping light power on the pulse width and the repetition frequency. FIG. 3A shows the dependence at a wavelength of 800 nm and FIG. 3B shows the dependence at 1060 nm, and both assume that the duration of the pulse train is 1 second, which is a typical measurement time.
As shown in FIG. 3, at the low repetition frequency, the allowable pumping light power decreases (and therefore the SN ratio decreases). For this reason, the repetition frequency is preferably 10 kHz or more, whereby the reduction in allowable power can be suppressed to 5 dB or less. Furthermore, the repetition frequency is preferably 50 kHz or more, so that a reduction in allowable power can be avoided. Note that (Requirement 3) is a limiting factor in the low frequency region where the allowable power increases with the repetition frequency, and (Requirement 2) is a limiting factor in the high frequency region where the allowable power is constant with respect to the repetition frequency.

  FIG. 4 shows the relationship between the allowable power P and the wavelength λ when the repetition frequency is 50 kHz or more. The allowable power P is expressed by the following equation.

  As will be described later, in the present invention, the wavelength of the excitation light is preferably 700 to 1100 nm. Among them, the wavelength of 1050 nm to 1100 nm is particularly preferable because the allowable power is high and the risk to the living body is relatively low.

On the other hand, the pulse width τ achievable decreases as 1 / f _r with increasing repetition frequency f _r, too small pulse width, since the spread spectrum of the Brillouin scattered light is not preferable. It is known that spread spectrum occurs when the pulse width is below the acoustic lifetime of the object to be measured. The acoustic lifetime τ _a is determined by the Brillouin gain line width Δf _B

It is expressed. According to Non-Patent Document 2, it is reported that Δf _B = 0.65 GHz for a tissue sample of the lens edge of a human eye, and Δf _B = 0.84 GHz for a tissue sample of the lens nucleus. The measurement conditions are λ = 488 nm and n × sin (θ / 2) = sin (π / 4). On the other hand, the refractive index of the crystalline lens is known to be about 1.41. Therefore, when measuring by backscattering as in the present invention, from the formula [Equation 3],

Therefore, the pulse width τ is

It is preferable to satisfy. As will be described later, the preferred wavelength range in the present invention is 700 to 1100 nm, so the pulse width is preferably 0.28 ns or more.
Therefore, preferable ranges for the repetition frequency f _r and the pulse width τ are f _r > 50 kHz, τ> 0.28 ns, and f _r τ <1, which are shown in FIG. By using a pulse parameter in this range, the SN ratio can be maximized in a range where no optical damage occurs, and a decrease in frequency accuracy due to the spread of the scattered light spectrum can be prevented.

  When the fundus 302 is to be measured as in this example, the wavelength of the excitation light 101 is preferably 700 to 1100 nm. When the wavelength is shorter than 700 nm, the depth of penetration due to light absorption by the retinal pigment epithelium and tissue damage due to photochemical action may occur. At wavelengths longer than 1100 nm, light does not reach the fundus blood vessels sufficiently due to light absorption by the aqueous humor. By using a wavelength of 700 to 1100 nm, these problems can be avoided.

  Excitation light 101 emitted from the laser light source 10 enters the optical system 20 via lenses 104a and 104b and a pinhole 105 for constituting a confocal optical system. The optical system 20 adjusts the spot position (irradiation position) of the excitation light 101 three-dimensionally with the movable mirrors 201 a and 201 b and the movable lens 202, and irradiates the measurement target 30.

The measurement object 30 is preferably an arterial wall of an arteriole of the fundus 302, for example, so that the elasticity of the blood vessel can be diagnosed. In cardiovascular arteries such as hypertension, it is known that morphological changes of the fundus arterioles occur, but elasticity changes occur in many blood vessels in advance of morphological changes, so the diagnosis of elasticity is an early stage of cardiovascular disease. It is effective for diagnosis.
For example, by measuring the Brillouin frequency shift or line width value of the fundus arteriole of a healthy person as a normal range for each gender and age, and determining whether the value in the subject belongs to the normal range by the computer 407 The risk of cardiovascular disease can be diagnosed.
In addition, one of the causes of dementia is known as lacunar infarction, which can cause infarction in the arterioles in the brain. Elasticity diagnosis is also effective for the diagnosis of dementia. It is also preferable to use blood in the arteriole as a measurement target, whereby blood pressure in the fundus can be diagnosed.

  FIG. 6A schematically shows the arrangement of the excitation light beam and the measurement object when the artery wall is the measurement object. In the figure, 101 is excitation light, 111 is a spot of the excitation light, 303 is an arteriole, 304 is a lumen, and 305 is surrounding tissue.

  Natural Brillouin scattering occurs in the measurement object irradiated with the excitation light 101. If the ratio of the light power backscattered by natural Brillouin scattering to the pumping light power is the reflectance R, the reflectance R can be obtained from RW Boyd and K. Rzazewski, Phys. Rev. A, Vol. 42, pp. 5514-5521, (1990) is given by

  Here, g is a Brillouin gain coefficient, h is a Planck's constant, ν is an optical frequency, L is an interaction length, and A is a beam cross-sectional area. <N> is the phonon number,

Given in. k is the Boltzmann constant and T is the absolute temperature. From the above equation, the reflectance is inversely proportional to the beam cross-sectional area. For this reason, the excitation light is preferably a zero-order Gaussian beam. The beam radius w (z) of the Gaussian beam is expressed by the following equation.

Here, z is the optical axis direction coordinate with the spot position as the origin, n is the refractive index of the measurement object, and w ₀ is the beam waist radius. As shown in the above equation, since the spot diameter changes in the optical axis direction in the Gaussian beam, it is necessary to replace the beam cross-sectional area A in the above equation [Equation 11] with the effective beam cross-sectional area A _eff of the following equation.

From the above formula, when w ₀ → 0 or L → ∞, the reflectivity is maximum and ideal, but in reality, L is limited by the object to be measured, and w ₀ also takes a finite value, so it is ideal. Compared with the case, the reflectance decreases.

  When the fundus arteriole 303 is the measurement target, the interaction length L is about 100 μm and the refractive index n is about 1.41, so the rate of decrease in reflectance is as shown in FIG. As shown in FIG. 6B, the spot radius is preferably set to 3.0 μm or less, whereby the reduction rate of the reflectance (= the reduction width from the maximum value / maximum value) can be suppressed to 50% or less.

In order to realize such a small spot radius, it is preferable to use the compensation optical system 60.
Reference: B. Hermann, et al., Opt. Lett. Vol. 29, pp. 2142-2144, (2004). When the adaptive optics system is not used, the lens 301 and the optical system are used. In many cases, the spot diameter is 15 to 20 μm or more due to the above aberration, but the compensation optical system 60 improves the spot diameter to 5 to 10 μm.
The compensation optical system 60 includes a semi-transparent mirror 603 that branches scattered light from the measurement object 30, a wavefront sensor 602 that measures the wavefront of the scattered light, a deformable mirror 601 that modulates the wavefront of the excitation light, and the measurement results of the wavefront sensor 602. Is composed of a control signal 604 for controlling the deformable mirror 601 so that becomes a flat wavefront.

  In the present invention, the elasticity and viscosity at the spot position (irradiation position) are measured, and the position of the spot with respect to the reference point in the measurement object is measured. Thereby, even when a living body is used as a measurement target, it is possible to prevent a decrease in measurement accuracy due to movement such as pulsation.

  Elasticity / viscosity is measured by the spectrum analyzer 40, and spot position measurement is performed by the irradiation position measuring device 50. The measurement result is processed by the computer 407 and displayed on the display 70 as a two-dimensional image or a three-dimensional image.

The spectrum analyzer 40 photoelectrically converts the captured scattered light and measures the spectrum of the scattered light. An optical filter 401 for extracting the Brillouin scattered light, and the power of the Brillouin scattered light extracted by the optical filter 401. , A synchronization detector 403 which detects the synchronization signal 102 and stores it in the storage device 404 as a data signal 405 together with a measurement value by the photodetector 402, a storage device 404 and a computer 407.
The optical filter 401 makes the transmission wavelength variable, and extracts the spectrum of the Brillouin scattered light by changing the transmission wavelength. Scattered light enters the optical filter 401 via the semi-transparent mirror 103a on the optical path.
The storage device 404 has a different storage area for each irradiation position, and accumulates and stores the spectrum power of the scattered light.
The calculator 407 calculates the Brillouin frequency shift and the Brillouin line width from the spectrum of the scattered light accumulated in the storage device 404.

The irradiation position measuring device 50 captures an image of the fundus 302 and measures the irradiation position of the excitation light, a guide light source 502 for the imaging, and a laser that measures the distance between the optical system 20 and the measurement target 30. A range finder 503, a photodetector 504 that detects scattered light, and a calculator 505 that performs processing described later.
The guide light emitted from the guide light source 502 is combined with the excitation light 101 via the semi-transparent mirror 103b disposed on the optical path. The fundus image captured by the camera 501 enters the camera 501 via the semi-transparent mirror 103c disposed on the optical path. Laser light for measuring the distance by the laser distance measuring device 503 is incident on the laser distance measuring device 503 via the semi-transparent mirror 103d disposed on the optical path. Scattered light incident on the photodetector 504 enters the photodetector 504 via the semi-transparent mirror 103e disposed on the optical path.
The computer 505 includes image processing means for extracting feature points to be measured from an image photographed by the camera 501. The computer 505 has means for detecting a reference point in the depth direction from the distribution of scattered light power in the optical axis direction.

The measurement sequence is shown in FIG.
First, an image of the fundus 302 is taken by the camera 501 in the irradiation position measuring device 50 (first step: S1).

Second, feature points are extracted from the fundus image by the image processing means of the computer 505, and xy coordinates are defined using the feature points (second step: S2).
As a feature point, it is preferable to select a branch point of the optic disc or fundus blood vessel. Since these feature points have little temporal variation and low possibility of misrecognition, they are suitable for application to follow-up observation and treatment evaluation because they are highly reproducible even when repeated measurement is performed over a period of time. It is preferable to extract three or more feature points, and it is preferable to select such that spot positions exist inside a polygon having the feature points as vertices. Thereby, the spot position can be measured with high accuracy even when the displacement of the measurement target region is not spatially uniform.

Third, a region to be measured is selected (third step: S3).
According to the purpose of diagnosis, an artery, a vein, or a surrounding nerve tissue can be selected.

Fourth, the depth direction (z ′ direction) distribution of the elastic scattering (Rayleigh scattering) intensity is measured (fourth step: S4).
Since elastic scattering (Rayleigh scattering) occupies a large proportion of the scattered light power emitted from the measurement object, the intensity of elastic scattering (Rayleigh scattering) can be measured by measuring the scattered light with the photodetector 504. Further, the depth direction distribution can be measured by moving the movable lens 202 of the optical system 20.

Fifth, a reference point in the depth direction is extracted from the distribution in the depth direction of the elastic scattering (Rayleigh scattering) intensity (fifth step: S5).
As the reference point in the depth direction, it is preferable to select the retinal surface, the inner surface of the blood vessel, the retina, or the pigment epithelium interface. Since the contrast of the scattering intensity is high, the measurement reproducibility of the reference point is high. Here, the z ′ coordinate used to express the depth direction distribution is based on the position of the movable lens 202. By this measurement, the correspondence between the coordinate z ′ of the optical system and the tissue (retina, blood vessel, etc.) can be obtained.

However, if the measurement object can move during the measurement, it is necessary to acquire movement information in addition to the above information and correct the influence of the movement.
Therefore, the sixth, the distance between the measuring object and the optical system, measured by the laser range finder 503 (sixth step: S6), this value and z _0. Further, as will be described later, by measuring the distance z between the optical system and the measurement object during measurement, it is possible to obtain information on the movement (z−z ₀ ) of the measurement object. By adding this value to z ′ as an offset, it is possible to obtain measurement target coordinates that are not affected by movement. Since the laser distance measuring device 503 can measure in a short time, it is suitable for use in correcting such movement.

  Seventh, a target spot position is set using the measurement target coordinates defined in the steps so far (seventh step: S7).

Eighth, the fundus is photographed by the camera 501, the spot position and the feature point position are measured, and the xy position of the spot is measured (eighth step: S8).
At this time, it is preferable to measure the spot position of the guide light source 502 by multiplexing the guide light source 502 having a wavelength of 700 to 1000 nm with the excitation light 101. Accordingly, it is possible to use a camera 501 using silicon as a light receiving element that can realize high sensitivity at low cost.

  Ninth, the distance (z) between the optical system 20 and the measuring object 30 is measured using the laser distance measuring device 503 (9th step: S9).

Tenth, the measurement result is compared with the target position (tenth step: S10).
If there is a difference, the eighth step: feedback to the spot position adjustment in S8 to correct the spot position in real time (S10 ').

  Eleventh, the scattered light spectrum is measured by the spectrum analyzer 40 (11th step: S11).

12th, the spectrum is accumulate | stored in the memory | storage device 404 (12th step: S12).
The storage area for accumulation here is allocated for each spot position, and accumulation is performed according to the spot position measured in the ninth step: S9. Although the spectrum measurement can be performed by one pulse in principle, in practice, it is desirable to improve the S / N ratio by accumulating the measurement results of a large number of pulses because of the low signal level of natural Brillouin scattering. At this time, even if the spot position changes from the intended position due to the movement of the measurement object, the position is measured in real time by measuring the position in real time and accumulating it in the storage area of the storage device 404 allocated for each position. A decrease in accuracy can be suppressed.

Thirteenth, the frequency shift and the line width are calculated by the calculator 407 from the spectrum extracted by the optical filter 401 (13th step: S13).
In the spectrum analyzer 40, the Brillouin scattered light is extracted by the variable optical filter 401, the power thereof is measured by the photodetector 402, and the spectrum of the Brillouin scattered light is extracted by changing the transmission wavelength of the filter.

As another spectrum measurement method, optical heterodyne detection or an angular dispersion spectrometer can also be used. Although the relative position of the spot (position with respect to the measurement object) can change during spectrum measurement due to the movement of the measurement object, the relative position of the spot measured by the irradiation position measuring device 50 is made to correspond to the storage address and scattered. By accumulating the data signal 405 corresponding to the optical power for each spot position, it is possible to prevent a decrease in measurement accuracy due to movement.
Further, spectrum information can be recorded by making the transmission wavelength of the filter correspond to the address.

  Further, the pulsation signal obtained from the electrocardiograph 80 attached to the living body to be measured may be the address signal 406c, and the scattered light power may be recorded for each pulsation phase, thereby affecting the influence of the pulsation. It can be easily compensated.

  In addition, the spatial distribution of elasticity and viscosity can be measured by actively changing the irradiation position. At this time, assuming that the integration time is T, the integration at time T / m is set at each irradiation position, where m is an integer, as compared to the method of successively integrating the time T for each irradiation position (FIG. 8A). A method of performing this as m units (FIG. 8B) is preferable. In any method, since the integration time is T, the bandwidth Δf in the equation [6] giving the S / N ratio is the same, but in the case of FIG. 8A, the allowable excitation light power when the exposure time is T is In contrast, in the case of FIG. 8B, the allowable excitation light power when the exposure time is T / m is applied.

  FIG. 9 shows the allowable excitation light power as a function of exposure time when the repetition frequency is 50 kHz and the wavelength is 1060 nm. In order to increase the allowable excitation light power and increase the S / N ratio, it is preferable that the exposure time is short, and therefore m is preferably large. On the other hand, since it is necessary to adjust the irradiation position every time T / m, T / m is equal to or longer than the operation time of the irradiation position adjusting mechanism, thereby reducing the overhead for position adjustment. Is preferable. Since typical position adjustment is performed by a mirror or lens driven by a motor, T / m = 1 to 100 ms is preferable.

  The embodiment of the present invention has been described above, but the present invention is not limited to this example, and it goes without saying that various modifications are possible within the scope of the technical idea described in the claims. Yes.

The schematic diagram which shows an example of embodiment of the elastic-viscosity measuring apparatus which concerns on this invention. Extract from JIS C6802 regarding the maximum allowable exposure (MPE) of laser light incident on the eye. It is a graph which shows the dependence with respect to the pulse width and repetition frequency of permissible excitation light power, (a) shows the dependence in wavelength 800nm, FIG.3 (b) shows the dependence in 1060nm. The graph which shows the relationship with respect to wavelength (lambda) of the allowable power P when a repetition frequency shall be 50 kHz or more. The graph which shows the preferable range regarding the repetition frequency _fr and pulse width (tau). (A) The figure which shows typically the arrangement | positioning of an excitation light beam and a measurement object at the time of making an arterial wall into a measurement object, (b) The graph which shows the reflectance fall rate with respect to the spot radius at the time of making a fundus arteriole into a measurement object . The flowchart which shows the sequence of a measurement by the elastic viscosity measuring apparatus of FIG. It is a time chart which shows the relationship between the measurement position in the case of measuring an irradiation position actively, and an excitation light pulse, (a) is the system which accumulates time T one after another for every irradiation position, (b) makes m an integer. A method of performing integration in units of m, where the integration at time T / m is performed at each irradiation position as one unit is shown. The graph which shows the allowable excitation light power when a repetition frequency is 50 kHz and a wavelength is 1060 nm as a function of exposure time.

Explanation of symbols

10: Laser light source 20: Optical system 30: Measurement target 40: Spectrum analyzer (spectrum analysis means)
50: Irradiation position measuring device (condensing position measuring means)
60: adaptive optics system 70: display (image processing means)
80: electrocardiographs 201a, 201b: movable mirror (condensing position moving means)
202: Movable lens (condensing position moving means)
404: Storage device (storage means)
407: Computer 505: Computer (including image processing means)
501: Camera (imaging means)
602: Wavefront sensor (wavefront measuring means)

Claims (10)

An excitation laser light source for generating excitation light;
An optical system that collects the excitation light at the collection position of the measurement target and captures the scattered light generated in the measurement target;
An elastic viscosity measuring device comprising a spectrum analyzing means for measuring a spectrum of the scattered light that has been captured and calculating at least one of a Brillouin frequency shift or a Brillouin line width from the spectrum,
The elastic viscosity measuring apparatus, wherein the excitation light is a periodic optical pulse train, and the scattered light is detected in synchronization with the optical pulse train.   2. The elastic viscosity measuring apparatus according to claim 1, further comprising a condensing position measuring unit that measures a condensing position of the excitation light. The spectrum analysis means has storage means for accumulating the power of the spectrum of the scattered light and storing it in a different storage area for each condensing position,
The condensing position measuring means measures a change in the condensing position due to the movement of the measurement object,
3. The elasticity according to claim 2, wherein the spectrum power of the measured scattered light is accumulated and stored in a storage area of the storage unit corresponding to the condensing position measured by the condensing position measuring unit. Viscosity measuring device. An elastic viscosity measuring device that detects scattered light from a plurality of condensing positions almost simultaneously,
The optical system condenses the excitation light at a plurality of condensing positions in a time-sharing manner,
4. The elastic viscosity measuring device according to claim 1, wherein the spectrum analyzing unit integrates the power of the spectrum of scattered light from each condensing position.   5. The elastic viscosity measuring apparatus according to claim 1, wherein a spot radius of the excitation light at the condensing position is 3 μm or less. Wavefront measuring means for measuring the wavefront of scattered light from the measurement object;
An adaptive optics system for adjusting the wavefront of the excitation light,
6. The elastic viscosity measuring apparatus according to claim 1, wherein the adaptive optics system is controlled so that a wavefront measured by the wavefront measuring unit becomes flat. An imaging means for taking an image of the measurement object and measuring a condensing position of the excitation light;
Image processing means for extracting feature points of the measurement object from the image,
The elastic viscosity measuring device according to claim 1, wherein the condensing position is moved based on the feature point. Distance measuring means for measuring a distance in the optical axis direction between the optical system and the measurement object;
The elastic viscosity measuring apparatus according to claim 1, further comprising a calculator that extracts a reference point in the depth direction from the distribution of power of the scattered light in the optical axis direction. The measurement object is a fundus blood vessel,
The elastic viscosity measurement according to any one of claims 1 to 8, further comprising means for comparing at least one of a Brillouin frequency shift and a Brillouin line width of a scattered light spectrum from the fundus blood vessel with a measurement value of a healthy person. apparatus. The excitation light has a repetition frequency of f [kHz], a pulse width of t [ns], a wavelength of λ [nm], and an average power of P [dBm].
f> 50
t> 0.28
700 <λ <1100
P <0.02 (λ−700) −1.6
P <5.4
The elastic viscosity measuring device according to claim 1, wherein all of the conditions are satisfied.